Substrate specificity and domain functions of extracellular heparan sulfate 6-O endosulfatases, QSulf1 and QSulf2

doi:10.1074/jbc.M511902200

HOME

QUICK SEARCH:

	Author:		Keyword(s):
Year:		Vol:		Page:

A more recent version of this article appeared on February 24, 2006

This Article

	Full Text (Accepted Manuscript)
	All Versions of this Article: 281/8/4969 most recent M511902200v1
	Alert me when this article is cited
	Alert me if a correction is posted

Services

	Email this article to a friend
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Download to citation manager
	Request Permissions

Citing Articles

	Citing Articles via HighWire
	Citing Articles via Google Scholar

Google Scholar

	Articles by Ai, X.
	Articles by Emerson ., C. P.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Ai, X.
	Articles by Emerson ., C. P., Jr

Social Bookmarking

	What's this?

Papers In Press, published online ahead of print December 23, 2005
J. Biol. Chem, 10.1074/jbc.M511902200
Submitted on November 4, 2005
Accepted on December 23, 2005

Substrate specificity and domain functions of extracellular heparan sulfate 6-O endosulfatases, QSulf1 and QSulf2

Xingbin Ai, Anh-Tri Do, Marion Kusche-Gullberg, Ulf Lindahl, Ke Lu, and Charles P. Emerson . Jr

Boston Biomedical Research Institute, Watertown, MA 02472

Corresponding Author: emersonc{at}bbri.org

The extracellular sulfatases (Sulfs) are evolutionally conserved family of heparan sulfate (HS)-specific 6-O endosulfatases. These enzymes remodel the 6-O sulfation of cell surface HS chains to promote Wnt signaling and inhibit FGF signaling for embryonic tissue patterning and control of tumor growth. In this study we demonstrate that the avian HS endosulfatases, QSulf1 and QSulf2, exhibit the same substrate specifity towards a subset of trisulfated disaccharides internal to HS chains. Further, we show that both QSulfs associate exclusively with cell membrane and are enzymatically active on the cell surface to desulfate both cell surface and cell matrix HS. Mutagenesis studies reveal that conserved amino acid regions in the hydrophilic domains (HD) of QSulf1 and QSulf2 have multiple functions to anchor Sulf to the cell surface, bind to HS substrates and mediate HS 6-O endosulfatase enzymatic activity. Results of our current studies establish the HD of Sulf enzymes as an essential multifunctional domain for their unique endosulfatase activities, but also demonstrate their extracellular activity for desulfation of cell surface and cell matrix HS in the control of extracellular signaling for embryonic development and tumor progression.

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

W. C. Lamanna, M.-A. Frese, M. Balleininger, and T. Dierks
Sulf Loss Influences N-, 2-O-, and 6-O-Sulfation of Multiple Heparan Sulfate Proteoglycans and Modulates Fibroblast Growth Factor Signaling
J. Biol. Chem., October 10, 2008; 283(41): 27724 - 27735.
[Abstract] [Full Text] [PDF]

X. Ai, T. Kitazawa, A.-T. Do, M. Kusche-Gullberg, P. A. Labosky, and C. P. Emerson Jr
SULF1 and SULF2 regulate heparan sulfate-mediated GDNF signaling for esophageal innervation
Development, September 15, 2007; 134(18): 3327 - 3338.
[Abstract] [Full Text] [PDF]

D. H. Lum, J. Tan, S. D. Rosen, and Z. Werb
Gene Trap Disruption of the Mouse Heparan Sulfate 6-O-Endosulfatase Gene, Sulf2
Mol. Cell. Biol., January 15, 2007; 27(2): 678 - 688.
[Abstract] [Full Text] [PDF]